AB0352 IMPACT OF SEROLOGIC STATUS ON CLINICAL RESPONSES TO UPADACITINIB OR ABATACEPT IN PATIENTS WITH RHEUMATOID ARTHRITIS AND PRIOR INADEQUATE RESPONSE TO BIOLOGIC DMARDs: SUB-GROUP ANALYSIS FROM THE PHASE 3 SELECT-CHOICE STUDY
Authors: A. Rubbert-Roth, J. Sparks, A. Constantin, R. Xavier, Y. Song, J. Suboticki, R. M. Fleischmann
Journal: Annals of the Rheumatic Diseases (2022)

Background In patients with RA who had a prior inadequate response or intolerance to biologic DMARDs, the oral Janus kinase inhibitor, upadacitinib (UPA), demonstrated superiority in change from baseline in DAS28(CRP) and DAS28(CRP)&lt;2.6 at week 12 and improved responses across additional endpoints compared to abatacept (ABA) in the phase 3 SELECT-CHOICE study. Seropositive patients have been reported to respond better to treatment than seronegative patients. Objectives To evaluate clinical responses with UPA versus ABA among RA patients based on serologic status. Methods In SELECT-CHOICE (24-week, phase 3, double-blind, controlled trial), RA patients were randomized to oral UPA (15 mg once daily) or intravenous (IV) ABA (at day 1 and weeks 2, 4, 8, 12, 16, and 20; &lt;60 kg, 500 mg; 60-100 kg, 750 mg; &gt;100 kg, 1000 mg). 1 UPA patients also received IV placebo and ABA patients also received oral placebo. All patients continued stable background conventional synthetic DMARDs. Starting at week 12, background RA medications were adjusted or added if patients did not experience ≥20% improvement compared to baseline in tender and swollen joint counts at two consecutive visits. For this sub-group analysis, patients were categorized as follows: RF+ and ACPA+, RF+ and/or ACPA+, and RF- and ACPA-. Mean change from baseline in DAS28(CRP), Clinical Disease Activity Index (CDAI), ACR responses, HAQ-DI, patient’s assessment of pain, and Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F) were evaluated at weeks 12 and 24. Statistical inference was conducted using Chi-square tests or analysis of covariance (ANCOVA) with non-responder imputation or multiple imputation used for missing data and nominal P -values shown. Results Of the total population (N=612), the majority of patients were seropositive for RF and/or ACPA at baseline (80.4%) (Table 1). Most patients were female (~80%), ~55 years old, and one-third had previously experienced ≥2 biologic DMARDs. Mean change from baseline in DAS28(CRP) and CDAI were numerically higher with UPA vs ABA at weeks 12 and 24 across all sub-groups (Figure 1). Regardless of serologic status, UPA demonstrated numerically higher responses vs ABA for ACR 20/50/70 and proportions of patients in low disease activity and remission at both timepoints (Table 1). Mean change from baseline in the HAQ-DI and the patient’s assessment of pain was numerically higher with UPA compared to ABA across all sub-groups and timepoints (data not shown). Clinical responses were generally numerically higher at week 24 compared to week 12, and for the seropositive groups compared to the seronegative group, with both UPA and ABA. Table 1. Clinical Responses with UPA 15 mg or ABA in RA Patients Across Serologic Status Sub-Groups at Weeks 12 and 24 RF+ and ACPA+ (n=390) RF+ and/or ACPA+ (n=492) RF- and ACPA- (n=120) UPA n=189 ABA n=201 UPA n=242 ABA n=250 UPA n=61 ABA n=59 Proportion of Patients (%) (NRI) † Week ACR20 12 81* 71 79* 71 62 47 24 84 78 82 77 67 59 ACR50 12 51* 40 51** 40 26* 12 24 63* 53 63* 54 44 32 ACR70 12 23 16 24* 15 11 7 24 39* 28 40** 28 25 20 DAS28(CRP) ≤3.2 12 54*** 34 54*** 33 33** 10 24 65** 49 65** 50 54 37 DAS28(CRP) &lt;2.6 12 32*** 17 33*** 15 18* 5 24 46** 33 48*** 33 39 25 CDAI ≤10 12 42 39 43 39 33* 17 24 59 55 60 56 51 34 CDAI ≤2.8 12 10* 3 10** 3 2 0 24 23* 14 23** 14 11 12 * P &lt;0.05; ** P &lt;0.01; *** P &lt;0.001 UPA vs. ABA; nominal P -values are presented and not adjusted for multiple comparisons † NRI was used for missing data Conclusion Across serologic statuses, clinical responses with UPA 15 mg vs ABA were numerically higher at weeks 12 and 24 among RA patients with prior inadequate response or intolerance to biologic DMARDs. In addition, clinical responses were numerically higher for seropositive patients compared to seronegative patients across all endpoints assessed, although the seronegative group had a smaller sample size in this post-hoc analysis. Acknowledgements AbbVie funded these studies and participated in the study design, research, analysis, data collection, interpretation of data. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie. Disclosure of Interests Andrea Rubbert-Roth Speakers bureau: AbbVie, BMS, Chugai, Roche, Gilead, Janssen, Lilly, Sanofi, Amgen, Novartis, Consultant of: AbbVie, BMS, Chugai, Roche, Gilead, Janssen, Lilly, Sanofi, Amgen, Novartis, Jeffrey Sparks Consultant of: Bristol-Myers Squibb, Gilead, Inova Diagnostics, Optum, and Pfizer., Arnaud Constantin Speakers bureau: AbbVie, BMS, Galapagos, Janssen, Lilly, Novartis, Pfizer, Sanofi, and UCB, Consultant of: AbbVie, BMS, Galapagos, Janssen, Lilly, Novartis, Pfizer, Sanofi, and UCB, Ricardo Xavier Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jessica Suboticki Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Roy M. Fleischmann Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, and UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Novartis, Pfizer Inc, Regeneron, Roche, Sanofi-Aventis and UCB